oncotype dx ® breast cancer assay. 22 agenda introduction development of oncotype dx ® clinical...

OncoOncotypetype DX DX®®

Breast Cancer AssayBreast Cancer Assay

22

Agenda

• Introduction• Development of Oncotype DX®

• Clinical Studies– Validation studies

– Hormonal therapy benefit study (NSABP B-14)

– Chemotherapy benefit study (NSABP B-20)

– Node + study (SWOG 8814)

– Decision Impact Studies

• TAILORx

• Genomic Health Clinical Laboratory Experience

• Clinical Summary

33

Breast Cancer Treatment Planning: History

• Treatment planning for N–, ER+ disease is based on: – Traditional prognostic factors with limited

predictive power (tumor size, patient age) or poor reproducibility (tumor grade)

– IHC markers (eg, Ki-67) lacking standardization and validation

– Limited insight into relative benefits of chemotherapy for different individuals

Bundred. Cancer Treat Rev. 2001;27:137-142.

44

Breast Cancer Treatment Planning: Not Optimized

• Chemotherapy treatment for N–, ER+ disease– Many women are offered chemotherapy,

knowing that few benefit

– Prior to 2007, guidelines assumed all patients benefit equally

– Some patients are under-treated, many others are over-treated

55

• Age: 61

• ER: 95%

• PR: 95%

• Tumor Type: IDC

• Tumor Size: 0.6 cm*

• Tumor Grade: 2

• HER-2 neu Neg (FISH)

*Additional 6 mm on re-excision

What Would Your Treatment Strategy Be For This Patient?

www.adjuvantonline.com. Standard version 8.0. Accessed 8/07

http://www.adjuvantonline.com/

66

CLINICAL EXPERIENCE

RESULTS

36Recurrence Score =

Patients with a Recurrence Score of 36 in clinical validation study had an Average Rate of Distance

Recurrence at 10 years of 25% (95% CI: 19%–30%)

Recurrence Score: 36Average Rate of Distant Recurrence at 10 Yrs: 25%

77

Oncotype DX®: Unmet Clinical Need for Better Markers

Biopsyor

Resection

Optimize chemotherapy + local therapy +

hormonal therapy

Optimize local therapy and hormonal therapy

Robust markers

High risk/Large chemo benefit

Low risk/Little chemo benefit

88

Development and Validation of a 21-Gene Assay for N–, ER+, Tam+ Patients

Develop real-time RT-PCR method for paraffin block

Select candidate genes (250 genes)

Model building studies (N = 447, including 233 from NSABP B-20)

Commit to a single 21-gene assay

Validation studies in NSABP B-14 and Kaiser Permanente

YEAR

2001

2002

2002

2003

2003

Paik et al. N Engl J Med. 2004;351:2817-2826.

99

Oncotype DX® Technology: Final Gene Set Selection

Study Site NNode

StatusER

Status Treatment

NSABP B-20, Pittsburgh, PA

233 N– ER+ Tamoxifen (100%)

Rush University, Chicago, IL

78 >10 positive nodes

ER+/– Tamoxifen (54%)Chemotherapy

(80%)

Providence St. Joseph’s Hospital, Burbank, CA

136 N+/– ER+/– Tamoxifen (41%)Chemotherapy

(39%)

21 genes and Recurrence Score (RS)algorithm

Paik et al. SABCS 2003. Abstract #16. Cobleigh et al. Clin Cancer Res. 2005;11(24 Pt 1):8623-8631.

Esteban et al. Proc ASCO 2003. Abstract #3416.

ObjectiveGene expression and relapse-free interval correlations across three independent studies – testing 250 genes in 447 patients

1010

Oncotype DX® 21-Gene Recurrence Score (RS) Assay

PROLIFERATIONKi-67

STK15Survivin

Cyclin B1MYBL2

ESTROGENERPR

Bcl2SCUBE2

INVASIONStromelysin 3Cathepsin L2

HER2GRB7HER2

BAG1GSTM1

REFERENCEBeta-actinGAPDHRPLPO

GUSTFRC

CD68

16 Cancer and 5 Reference Genes From 3 Studies

Category RS (0 -100)Low risk RS <18

Int risk RS 18 - 30

High risk RS ≥ 31


RS = + 0.47 x HER2 Group Score - 0.34 x ER Group Score + 1.04 x Proliferation Group Score+ 0.10 x Invasion Group Score + 0.05 x CD68- 0.08 x GSTM1- 0.07 x BAG1

1111

Oncotype DX® Clinical Validation: RS as Continuous Predictor

0%

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Recurrence Score

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Low-Risk Group High-Risk Group Intermediate- Risk Group

95% CI

My RS is 30. What is the chance of recurrence within 10 years?

My RS is 30. What is the chance of recurrence within 10 years?


Clinical Validation:Clinical Validation:

The The NSABP B-14 Study*NSABP B-14 Study*

*Paik et al. N Engl J Med. 2004;351:2817-2826.

1313

• Objective: Prospectively validate RS as predictor of distant recurrence in N–, ER+ patients

• Design

– Multicenter study with prespecified 21-gene assay, algorithm, endpoints, analysis plan

Oncotype DX® Clinical Validation: Genomic Health – NSABP B-14

Randomized

Registered

Placebo—not eligible

Tamoxifen—eligible

Tamoxifen—eligible


1414

Oncotype DX® Clinical Validation:B-14 Results – Distant Recurrence

Distant Recurrence Over Time – All 668 Patients

Proportion Without Distant Recurrence at 10 years = 85%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 2 4 6 8 10 12 14 16

YearsPaik et al. N Engl J Med. 2004;351:2817-2826.

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Oncotype DX® Clinical Validation: B-14 Results – Distant Recurrence

Distant Recurrence for the three distinct cohorts identified

0%

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20%

30%

40%

50%

60%

70%

80%

90%

100%

0 2 4 6 8 10 12 14 16

Years

P <0.001

RS <18 n = 338

RS 18-30 n = 149

RS 31 n = 181


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1616

Oncotype DX® Clinical Validation:B-14 Results – Distant Recurrence

Risk Group % of 10-yr Rate of Patients Recurrence 95% CI

Low (RS <18) 51% 6.8% 4.0%, 9.6%

Intermediate (RS 18-30) 22% 14.3% 8.3%, 20.3%

High (RS ≥31) 27% 30.5% 23.6%, 37.4%

Test for the 10-year Distant Recurrence comparison between the low-and high-risk groups: P <0.001


1717

Oncotype DX® Clinical Validation: B-14 Results Multivariate Analysis Confirms Power of RS

Multivariate Cox Models: Age, Size + RS

P value95% CIHazard RatioVariable

<0.001(2.23, 4.61) 3.21Recurrence Score

0.231(0.86, 1.85)1.26Size >2.0 cm

0.084(0.48, 1.05)0.71Age ≥50

Age at surgery used as a binary factor: 0 = <50 yr, 1 = ≥50 yr.Clinical tumor size (CTS) used as a binary factor: 0 = ≤2 cm, 1 = >2 cm.Recurrence Score used as a continuous variable, with HR relative to an increment of 50 RS units.



Clinical Validation:Clinical Validation:

The The Kaiser Permanente StudyKaiser Permanente Study

Habel et al. Breast Cancer Res. 2006;May 31;8(3):R25.

1919

The Kaiser Permanente Study: Methods

Study Design

Study Population

Data Sources

Matched Case-Control

Kaiser Permanente patients <75 yr in 14 Northern California hospitals diagnosed with node-negative BC 1985-94, no chemotherapy (N = 4964)

Cases: Deaths from BC (n = 220)

Controls: Randomly selected, matched on age, race, diagnosis year, KP facility, tamoxifen (n = 570)

Cancer registry, medical records, archived diagnostic slides, and tumor blocks

Habel et al. Breast Cancer Res. May 2006.

2020

The Kaiser Permanente Study: Risk of BC Death at 10 Years: ER+, Tam+ Patients

10-yr 10-yr Absolute Absolute

Risk Classifier Risk1 Risk Kaiser NSABP B14

Recurrence Score Low (<18) 2.8% 3.1%

Intermediate (18-30) 10.7% 12.2% High (>31) 15.5% 27.0%

1Based on methods by Langholz and Borgan, Biometrics 1997;53:767-774.


2121

The Kaiser Permanente Study: Conclusions

• “The RS has now been shown to be strongly associated with risk of breast cancer-specific mortality among LN–, ER+, tam-treated patients participating in a clinical trial and among similar patients from the community setting.”

• “Combining Recurrence Score, tumor grade, and tumor size provides better risk classification than any one of these factors alone.”



Prediction of Tam Benefit:Prediction of Tam Benefit:NSABP B-14 Placebo andNSABP B-14 Placebo and

Tamoxifen Arms* Tamoxifen Arms*

*Paik et al. ASCO 2004. Abstract #510.

2323

Design

Objective: Determine whether the 21-gene RS assay provides predictive information for patients who were treated with tamoxifen (likelihood of recurrence)

Tamoxifen Benefit and Oncotype DX™

NSABP B-14 Tam Benefit Study in N–, ER+ Patients

Randomized

Placebo-Eligible

Tam-Eligible

Paik et al. ASCO 2004. Abstract #510.

2424

All Patients (N = 645)

0 2 4 6 8 14 16

Years

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

PlaceboTamoxifen

1210

B-14 Overall Benefit of Tamoxifen


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2525

B-14 Benefit of TamoxifenBy Recurrence Score Risk Category

Low Risk (RS<18)N

171142

Int Risk (RS 18-30)N8569

High Risk (RS≥31)1

N9979

Interaction P = 0.06

0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

PlaceboTamoxifen

1210

0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

PlaceboTamoxifen

1210 0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

PlaceboTamoxifen

1210


1 The results should not be used to conclude that tamoxifen should not be given to the high-risk group

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2626

Analysis of Placebo and Tam-Treated Patients in NSABP B-14

• Results– Subset of Oncotype DX® genes is prognostic

• 5 proliferation genes – Cyclin B1, Ki-67, MYBL2, Survivin, STK15

• PR

– Quantitative measurement of the ER gene expression by the Oncotype DX® assay predicts the benefit of tamoxifen

– Quantitative ER and Recurrence Score are only modestly correlated


2727

Analysis of Placebo and Tam-Treated Patients in NSABP B-14

• Conclusions– RS combines prognostic and predictive

factors into one assay report

– RS performance is derived from measurement of expression of each of the 21 genes on a continuous scale with high precision and reproducibility



Prediction of Chemo Benefit:Prediction of Chemo Benefit:

NSABP B-20 StudyNSABP B-20 Study**

*Paik et al. J Clin Oncol. 2006;24:3726-3734

2929

Chemotherapy Benefit and Oncotype DX®

Design

Objective: Determine the magnitude of the chemo benefit as a function of the 21-gene RS assay

Randomized

Tam + MF

Tam + CMF

Tam

NSABP B-20 Chemo Benefit Study in N–, ER+ Pts

Paik et al. J Clin Oncol. 2006;24:3726-3734.

3030

B-20 Results

0 2 4 6 8 10 12

Years

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

All Patients

Tam + ChemoTam P = 0.02

N Events 424 33 227 31 P

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Tam vs Tam + Chemo – All 651 Patients

Paik et al. J Clin Oncol. 2006.

4.4% absolute

benefit from tam + chemo at 10 years

3131

B-20 Results: Tam vs Tam + Chemo

28% absolute benefit from tam + chemo


0 2 4 6 8 10 12

Years

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

DR

FS

Low R isk Patients (R S < 18) T am + C hemo T am

p = 0.61

0 2 4 6 8 10 12

Years

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

DR

FS

Int Risk (RS 18 - 30) Tam + C hem o Tam

p = 0.39Low RS

0 2 4 6 8 10 12

Years

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

DR

FS

H igh R isk Patients (R S 31) T am + C hemo T am

p < 0.001

Int RS

High RS

High Risk Patients (RS≥31) N Events

TAM + Chemo 117 13 TAM 47 18

Low Risk Patients (RS<18) N

Events

TAM + Chemo 218 8 TAM 135 4

Int Risk Patients (RS 18-30) N Events

TAM + Chemo 89 9TAM 45 4

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could we move these pvalues into the puicture?

3232

LowRS <18

IntRS 18-30

HighRS ≥31

0 10% 20% 30% 40%

B-20 Results: Absolute % Increase in Proportion Distant Recurrence-Free at 10 Years

n = 353

n = 134

n = 164

% Increase in Proportion Distant Recurrence-Free at 10 Yrs (mean ± SE) Paik et al. J Clin Oncol. 2006.

3333

Summary of Treatment Benefit Related to RS and Breast Cancer Death in NSABP B-14 and B-20

B14 No Tam

B14 Tam

B20 Tam

B20 Tam + CT

Low Risk (RS < 18)Intermediate Risk (RS 18 - 30)HIgh Risk (RS > 31)

10 Yr Absolute Risk BC Death (%) (95% CI)

0 5 10 15 20 25 30 35 40

NO SYSTEMIC RX

HORMONAL RX

HORM + CHEMO

3434

Largest Tamoxifen Benefit Observed in Low- and Intermediate-Risk Recurrence Score Groups

B14 No Tam

B14 Tam

B20 Tam

B20 Tam + CT

Low Risk (RS < 18)Intermediate Risk (RS 18 - 30)HIgh Risk (RS > 31)


0 5 10 15 20 25 30 35 40

NO SYSTEMIC RX

HORMONAL RX

HORM + CHEMO

TAMOXIFEN BENEFIT

3535

Largest Chemotherapy Benefit Observed in High-Risk Recurrence Score Group

B14 No Tam

B14 Tam

B20 Tam

B20 Tam + CT

Low Risk (RS < 18)Intermediate Risk (RS 18 - 30)

HIgh Risk (RS > 31)


0 5 10 15 20 25 30 35 40

NO SYSTEMIC RX

HORMONAL RX

HORM + CHEMO CHEMOTHERAPYBENEFIT

3636

Recurrence Score in N-, ER+ patients

Standardized Quantitative Oncotype DX Assay

0%

5%

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40%

0 5 10 15 20 25 30 35 40 45 50

Recurrence Score

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rs

Low Risk Group High Risk Group Intermediate Risk Group

1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006 3) Paik et al JCO 2006, 4) Gianni et al JCO 2005

Lower RS’s•Lower likelihood of recurrenceLower likelihood of recurrence•Greater magnitude of TAM benefitGreater magnitude of TAM benefit•Minimal, if any, chemotherapy benefitMinimal, if any, chemotherapy benefit

Higher RS’s•Greater likelihood of recurrenceGreater likelihood of recurrence•Lower magnitude of TAM benefitLower magnitude of TAM benefit•Clear chemotherapy benefitClear chemotherapy benefit

Correlation of RS with traditional prognostic factors including age,

tumor size, and tumor grade

Results from NSABP B20 Results

3838

A:<40 B:40-49 C:50-59 D:>=60

Age

0

20

40

60

80

100

Re

curre

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.Sco

re

< 40 40 - 49 50 - 59 ≥ 60

Patient Age

Rec

urre

nce

Sco

re

N=63 N=226 N=166 N=196

41% 24% 28% 19%

14% 21% 22% 21%

44% 55% 50% 60%

p=0.018

A:<40 B:40-49 C:50-59 D:>=60

Age

0

20

40

60

80

100

Re

curre

nce

.Sco

re

< 40 40 - 49 50 - 59 ≥ 60

Patient Age

Rec

urre

nce

Sco

re

N=63 N=226 N=166 N=196

41% 24% 28% 19%

14% 21% 22% 21%

44% 55% 50% 60%

A:<40 B:40-49 C:50-59 D:>=60

Age

0

20

40

60

80

100

Re

curre

nce

.Sco

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< 40 40 - 49 50 - 59 ≥ 60

Patient Age

Rec

urre

nce

Sco

re

N=63 N=226 N=166 N=196

41% 24% 28% 19%

14% 21% 22% 21%

44% 55% 50% 60%

p=0.018

NSABP B20 Results: Many Younger Patients Have Low Recurrence Scores


3939

A:<= 1cm B:1.1-2.0cm C:2.1-4.0cm D:>= 4.1cm

Clinical.Tumor.Size

0

20

40

60

80

100

Re

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.Sco

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Rec

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Sco

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≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm > 4 cm

Clinical Tumor Size

16% 25% 30% 33%

20% 19% 23% 21%

64% 56% 46% 46%

N=110 N=318 N=196 N=24

p=0.001

A:<= 1cm B:1.1-2.0cm C:2.1-4.0cm D:>= 4.1cm

Clinical.Tumor.Size

0

20

40

60

80

100

Re

curre

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.Sco

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Rec

urre

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Sco

re

≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm > 4 cm

Clinical Tumor Size

16% 25% 30% 33%

20% 19% 23% 21%

64% 56% 46% 46%

N=110 N=318 N=196 N=24

A:<= 1cm B:1.1-2.0cm C:2.1-4.0cm D:>= 4.1cm

Clinical.Tumor.Size

0

20

40

60

80

100

Re

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.Sco

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Rec

urre

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Sco

re

≤ 1 cm 1.1 - 2 cm 2.1 - 4 cm > 4 cm

Clinical Tumor Size

16% 25% 30% 33%

20% 19% 23% 21%

64% 56% 46% 46%

N=110 N=318 N=196 N=24

p=0.001

NSABP B20 Results: Many Small Tumors Have Intermediate to High RS


4040

A:Well B:Moderate C:Poor

Tumor.Grade.C

0

20

40

60

80

100

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Sco

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Well

Tumor Grade (Pathologist B)

Moderate Poor

N=119 N=340 N=190

5% 12% 61%

12% 24% 19%

83% 64% 19%

p<0.001


Tumor.Grade.C

0

20

40

60

80

100

Re

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.Sco

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Rec

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Sco

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Well


Moderate Poor

N=119 N=340 N=190

5% 12% 61%

12% 24% 19%

83% 64% 19%


Tumor.Grade.C

0

20

40

60

80

100

Re

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.Sco

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Rec

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Sco

re

Well


Moderate Poor

N=119 N=340 N=190

5% 12% 61%

12% 24% 19%

83% 64% 19%

p<0.001


Tumor.Grade.A

0

20

40

60

80

100

Re

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.Sco

re

Rec

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Sco

re

Well

Tumor Grade (Site)

Moderate Poor

12% 22% 42%

16% 22% 22%

73% 56% 36%

N=77 N=339 N=163

p<0.001


Tumor.Grade.A

0

20

40

60

80

100

Re

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.Sco

re

Rec

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nce

Sco

re

Well

Tumor Grade (Site)

Moderate Poor

12% 22% 42%

16% 22% 22%

73% 56% 36%

N=77 N=339 N=163


Tumor.Grade.A

0

20

40

60

80

100

Re

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.Sco

re

Rec

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nce

Sco

re

Well

Tumor Grade (Site)

Moderate Poor

12% 22% 42%

16% 22% 22%

73% 56% 36%

N=77 N=339 N=163

p<0.001

NSABP B20 Results: Significant Proportion of High-Grade Tumors Have Low RS

Grading by pathologist at local clinical trial site

Grading by pathologist at central lab


Prospective multi-center study of the impact of the 21-gene Recurrence Score (RS) assay on medical

oncologist (MO) and patient (pt) adjuvant breast cancer (BC) treatment selection

Shelly S. Lo1, John Norton1, Patricia B. Mumby1, Jeffrey Smerage2, Joseph Kash3, Helen K. Chew4, Daniel Hayes2,

Andrew Epstein5, Kathy S. Albain1

1Loyola University, Maywood IL, 2University of Michigan, Ann Arbor MI, 3Edward Hospital, Naperville IL, 4UC Davis,

Sacramento CA, 5Mount Sinai Medical Center, New York NY

ASCO 2007, Abstract #577

4242

Background

• There is little data regarding the impact of the RS on medical oncologist (MO) and patient (pt) decision making. A multi-center study was designed to prospectively examine whether the RS can affect MO and pt adjuvant treatment selection.


4343

Methods

• 17 MOs at 1 community and 3 academic practices participated. Each participating MO consecutively offered enrollment to eligible women with N-, ER+ BC.

• Each participating MO and consenting patient completed pre- and post-RS assay questionnaires.

• MOs stated their adjuvant treatment recommendation and confidence in it pre and post RS assay.

• Pts indicated treatment choice pre and post RS assay. In addition, patients completed measures for quality of life, anxiety, and decisional conflict pre and post assay.

• RS assay results were returned to MO and shared with pt for routine clinical care.


4444

Change in MO Treatment Recommendation by RS

MO

Treatment Recomm.

Pre-RS Post- RS

Number (%) Mean RS Number (%)

Mean RS

CHT 42 (47.2%) 21 23 (25.8%) 29

HT alone 46 (51.7%) 18 60 (67.4%) 16

Equipoise 1 (1.1%) 19 6 (6.7%) 19


4545

MO Treatment Recommendations Changed 31.5% of the Time

MO Pre to Post-RS Assay Treatment Recommendation

Number of Cases(%)

CHT to HT 20 (22.5)

HT to CHT 3 (3.4)

CHT or HT to Equipoise 5 (5.6)

Treatment plan did not change

61 (68.5)

Total 89 (100)

Treatment recommendation changed for 28 (31.5%) cases after results of RS Assay known.

The most common change was from a recommendation of CHT to HT in 22.5% of cases


4646

Other Findings

• Confidence was increased in 76% of the MO recommendations.

• RS Assay impacted patient adjuvant treatment decisions

• 95% of patients were glad they had the test performed• 12 (13.5%) patient treatment decisions did not match

their MO treatment recommendation. This may be due to:– Patients choosing different treatment option than that

recommended– Inadequate communication between MOs and pts– Patient misunderstanding of survey question


4747

Conclusions

• RS Assay changed physician adjuvant treatment recommendation 31.5% of the time

• Results from the RS assay were associated with less adjuvant chemotherapy administration

– The most common treatment recommendation change for MO was changing recommendation from CHT to HT in 22.5% of cases

– Of the 6 pts whose physicians thought their RS represented equipoise, 1 pt chose chemotherapy, 3 chose HT, 1 chose observation, and 1 understood the concept of equipoise.

• Results of the RS Assay increased physician confidence in treatment recommendation


TAILORxTAILORx(PACCT-1 Trial)(PACCT-1 Trial)

Sponsored by NCISponsored by NCI Administered by ECOG Administered by ECOG

Participating cooperative groups include ECOG, SWOG, NCCTG, CALGB, NCIC,

ACOSOG, and NSABP

4949

Trial Assigning IndividuaLized Options for Treatment (Rx) (TAILORx)

• Premise– Integration of a molecular profiling test (Oncotype DX®)

into the clinical decision-making process

• Potential Implications– Reduce chemotherapy overtreatment in those likely to

be appropriately treated with hormonal therapy alone– Reduce inadequate treatment by identifying individuals

who derive great benefit from chemotherapy– Evaluate benefit of chemotherapy where uncertainty

still exists about its utility

5050

TAILORx: Scientific Rationale for NCI and Breast Intergroup Selecting

Oncotype DX® Assay for First PACCT trial

1. Validated prognostic test for tamoxifen-treated patients – Predictive of distant recurrence

– May be used as categorical or continuous variable

– Paik et al. NEJM, 2004

2. Also validated in population-based Kaiser study – Habel et al. Breast Cancer Research, May 2006

3. Lower RS predictive of tamoxifen benefit – Paik et al. ASCO 2005, abstr 510

4. Higher RS predictive of chemotherapy benefit– Paik et al. JCO, August 2006

5. Correlates more strongly with outcome than Adjuvant! – Bryant et al. St. Gallen, 2005

6. Predictive of local recurrence in tam-treated patients – Mamounas, SABCS 2005, abstr 29

Sparano, Clinical Breast Cancer, 2006Sparano, ASCO Educational Book 2007

5151

0%

5%

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40%

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Low Risk Group High Risk Group Intermediate Risk Group

TAILORx PrimaryStudy Group

5252

Schema: TAILORx

Node-Neg, ER-Pos Breast CancerNode-Neg, ER-Pos Breast Cancer

RS <10HormoneTherapyRegistry

RS <10HormoneTherapyRegistry

RS 11-25Randomize

Hormone Rxvs

Chemotherapy + Hormone Rx

RS 11-25Randomize

Hormone Rxvs

Chemotherapy + Hormone Rx

RS >25Chemotherapy

+Hormone Rx

RS >25Chemotherapy

+Hormone Rx

Oncotype DX® AssayOncotype DX® AssayRegister

Specimen banking

Primary study group

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Study Design: Primary Objectives

• To determine whether adjuvant hormonal therapy (ie, experimental arm) is not inferior to adjuvant chemohormonal (standard arm) for patients in the “primary study group” (Oncotype DX® RS 11-25)

• To create a tissue and specimen bank for patients enrolled in this trial to learn more about breast cancer

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TAILORx: Key Points

• Participating groups– ECOG, SWOG, NCCTG, CALGB, NCIC, ACOSOG, and NSABP

• Adjuvant therapy– Choice of hormonal and/or chemotherapy regimen is at

discretion of treating physician

• Other trials– May enroll on other CTSU or other cooperative group studies

if treatment assignment on other trial is consistent

• Payment for the Oncotype DX Assay– Genomic Health will assist in securing reimbursement for

patients who have health insurance– By agreement with NCI to avoid bias in enrollment in the trial,

patients who are uninsured or who have copayments or deductibles will not be responsible for the cost of the Oncotype DX®

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Oncotype DX® Extensively Studied:Study Experience in >3300 Patients

*Published studies

Study Type No. PtsProvidence Exploratory 136

Rush* Exploratory 78

NSABP B-20 Exploratory 233

NSABP B-14* Prospective 668

MD Anderson* Prospective 149

Kaiser Permanente* Prospective Case-Control 790 Cases/Controls

NSABP B-14 Prospective Placebo vs Tam 645

Milan* Exploratory 89

NSABP B-20* Prospective Tam vs Tam+Chemo 651

ECOG 2197* Exploratory and Prospective 776

SWOG 8814 Prospective Tam vs Tam+Chemo 367

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Recurrence Score in N-, ER+ patients

Conclusions

1) Paik et al NEJM 2004, 2) Habel et al Breast Cancer Research 2006 3) Paik et al JCO 2006, 4) Gianni et al JCO 2005

Lower RS’s• Lower likelihood of recurrence• Greater magnitude of TAM benefit• Minimal, if any, chemotherapy benefit

Higher RS’s• Greater likelihood of recurrence• Lower magnitude of TAM benefit• Clear chemotherapy benefit

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Genomic Health Today

• Physician Usage and Adoption– 65,000+ Oncotype DX® test results delivered*

– >7,500 physicians have ordered the test*

• Reimbursement for Oncotype DX– Coverage for Medicare patients

– Coverage >90% of privately insured lives

*As of August 5, 2008

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Conclusions

• The Oncotype DX® Recurrence Score assay predicts the likelihood of adjuvant chemotherapy benefit

• It also is a prognostic assay for the risk of distant recurrence at ten years assuming five years of adjuvant tamoxifen treatment

• Oncotype DX® Recurrence Score assay shows consistent results across multiple independent studies

oncotype dx ® breast cancer assay. 22 agenda introduction development of oncotype dx ® clinical...

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